WO1981000116A1 - Methode de purification d'interferon et analyse d'interferon - Google Patents

Methode de purification d'interferon et analyse d'interferon Download PDF

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Publication number
WO1981000116A1
WO1981000116A1 PCT/US1980/000842 US8000842W WO8100116A1 WO 1981000116 A1 WO1981000116 A1 WO 1981000116A1 US 8000842 W US8000842 W US 8000842W WO 8100116 A1 WO8100116 A1 WO 8100116A1
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WO
WIPO (PCT)
Prior art keywords
interferon
odd
computed
states
activity
Prior art date
Application number
PCT/US1980/000842
Other languages
English (en)
Inventor
W Robinson
J Hurtt
Original Assignee
United States Res Corp
W Robinson
J Hurtt
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by United States Res Corp, W Robinson, J Hurtt filed Critical United States Res Corp
Priority to AU62259/80A priority Critical patent/AU6225980A/en
Publication of WO1981000116A1 publication Critical patent/WO1981000116A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6866—Interferon

Definitions

  • This invention relates to the use of multiplexing techniques (computers) and sonication factors (wave energy) for the large scale production, purification and rapid analysis of the Interferons.
  • Wave energy is injected into medium in containers (electronic electrochemical monitoring and controlling devices) equipped with associated electronics controlled by computers, thus affording the opportunity to standardize procedures for the dissociation of interferon from cells and other debris, while facilitating the rapid anlysis of said interferon.
  • the recent availability of sufficient quantities of human interferon for clinical trials has marie possible the demonstration that interferon is effective in the treatment of Hepatitis B, respiratory virus infections, Varicella-Zoster and other herpes virus infections, and perhaps human cancer.
  • the quantum and wave mechanics of the induction of the three translation regulatory enzymes by the interferons provide a convenient model system to compute and to measure the heterogeniety of interferon induced activity.
  • the dosage necessary for the induction of protein kinase (PKI) molecular weight 67,000, is shown to be similar to that for the development of the antiviral state.
  • the end point of the assay can be measured directly by a reduction in the 3'ield in infectivity to a significant level.
  • effects en the ir.rune system such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • effects on cell surface antirens such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • effects on cell surface antirens such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • effects on cell surface antirens such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • effects on cell surface antirens such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • effects on cell surface antirens such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • effects on cell surface antirens such as inhibition and stimulation of antibody formation, m ⁇ croprare activation, and inhibitory effects on cell mediated immunity
  • our invention consisting of a combination of manual and automatic m.anuevers, is designed to produce, purify and rabidly analyze the interferons.
  • process consisting of a combination of manual and automatic m.anuevers, is designed to produce, purify and rabidly analyze the interferons.
  • Spectrophotometric digital computers may be interfaced for routine sample analysis, for data acquisition, and online control; A computerized operation was designed to prove the principles of measurement and controls by conductivity determinations.
  • a critical parameter for the separation cells is the position of the interface between the cells. The position of the interface is sensed optically. Fiber optic rods for instance can carry light through a designated area of a container. The light is picked up by another optic device positioned near by, and then deteched by a photodiode. An electric circuit detects the light pulse and produces a d.c. voltage is measured by the interface position and is used as a control signal.
  • Digital analytical accessories are currently being used in chromosomal studies. Rapid analysis can then be achieved with the interface of a 3-D thermolumfinescent device.
  • a scanning monochromator and a highly sophisticated temperature programmer and controller are necessary to fully utlize the spectra of the emitted light. Between 50,000-100,000 data points are plotted on each sample. The data is then automatically analyzed and prepared for plotting out as a function of wave length and sample temperature. They are presented graphically end facilitate rapid and thorough analysis of the data. The details of the components of the process will be described in connection with the accompanying drawing, in which fig. 1, shows a flow chart for the production, purification and rapid analysis of interferon.
  • the equipment is arranged so that their constant monitoring and control is performed by a spectrophotometric (digital) computer. Purification to apparent homogeneity may be accomplished by liquid and gas chromatography. Final confirmation of the contaminant levels should be determined by 3-D thermoluminescence procedures. Descript.ion of the drawing;
  • step (j) waiting a predetermined time then repeating step (f) ....
  • White blood cells obtained fror normal donors may be placed in a leukochronometer 1 for quantitation.
  • the crude interferon is then placed in containers (electronic electrochemical monitoring and controlling device (s) equipped with associated electronics that utilize combined or separate A.C.D.C. audio and radio frequency (wave energy) to promote medium agitation (oarticle separation) by dissociation of the elements or molecules (cells , debris ) in suspension solution.
  • the medium is then innoculated with viruses, mitogens (staphlocccccus anterotoxin A or other interferon inducers. Casein is then added to rpcvide a simplier mileu from which to isolate the interferon. After agitation for 35 minutes the broth is incubated for approx., 16 hours. Pilot experiments have yielded titers of 10,000 to 20,000 units/ml. Concentration and intital fractionation processes should be carried out at temperatures of 0-4°C.
  • urea (1.5g) is added to the interferon concentrate and then the solution can be applied to a column of senhadex G-103 fine (2.5 ⁇ 90 cm).
  • the columns can be ⁇ luted at ph.7.5 at room temperatures at a flow rate of 0.5 ml/minute (apnrox).
  • High performance liquid chromatography techniques may be employed to obtain purified interferon.
  • the analysis can be performed on a chromatographic mass spectrometer on-line with a computer. Chromatography can be performed on coiled columns. Mass spectrometer operational parameters include: molecular sparator, 230°C; ion source, 260°C; electron voltage, 22.5 eV; scans may be taken every 5s from mass 0 to 410.
  • the relative labelled to unlabelled ion intensity (2H/1H rotio) for each amino acid can be determined in the following way: the maximum intensity of a significant ion from the unlabelled amino acid is found; the intensities above a specified background value of this spectral line are integrated.
  • Isotope ratio determined can be used as the quantitating technique via multiple internal standards.
  • the exact compostition of a deuterated amino acid mixture can be determined against a standard amino acid calibration mixture and in turn the protein amino acid composition is determined against the deuterated amino acid mixture.
  • the mixture of deuterated amino acids with known concentrations can be used to measure the relative concentration of unlabelled interferon amino acid.
  • a reference is needed for use in collaborative studies on interferon standards in which several laboratories participate and where a common assay method must be used.
  • the assay must be reproducible and the end products objective and unequivocal.
  • the end point of the assay should be measured directly by a reduction in yield of virus infectivity to a significant level, between 0.5 log 10 and 1.0 log 10 compared to control cultures not treated with interferon.
  • endpoints are available in a number of methods; (1) those which provide for obtaining continuous, whole-number observations, including per centage reduction methods (the number of lytic plaques, flcrescent or transferred foci, amount of dye uptake enzyme yield, radiolabeled precursor incorpor ation and quantitive haemadsorption) and (2) these which provide for obtaining discontinuous observations, such as reduction in logarhythms of haemagglutin yield.
  • per centage reduction methods the number of lytic plaques, flcrescent or transferred foci, amount of dye uptake enzyme yield, radiolabeled precursor incorpor ation and quantitive haemadsorption
  • discontinuous observations such as reduction in logarhythms of haemagglutin yield.
  • bio ⁇ ssay has been designed to measure disease dependent glycolytic activity, whose presence and titers are alterably controlled by interferons. By monitoring the rate of glycolysis in standard calibration medium one should be able to measure the rate of glucose/interfercn activity, while elucidating the independence of the carbohydrate and the fatoxidizing systems.

Abstract

Methode de purification d'interferon a partir d'un echantillon brut d'interferon avant son analyse pour determiner la purete et la structure d'interferon dans l'echantillon brut.
PCT/US1980/000842 1979-07-05 1980-07-07 Methode de purification d'interferon et analyse d'interferon WO1981000116A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU62259/80A AU6225980A (en) 1979-07-05 1980-07-07 Method for the purification and analysis of interferon

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5505379A 1979-07-05 1979-07-05
US55053 1979-07-05

Publications (1)

Publication Number Publication Date
WO1981000116A1 true WO1981000116A1 (fr) 1981-01-22

Family

ID=21995266

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1980/000842 WO1981000116A1 (fr) 1979-07-05 1980-07-07 Methode de purification d'interferon et analyse d'interferon

Country Status (2)

Country Link
EP (1) EP0031381A1 (fr)
WO (1) WO1981000116A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7588755B1 (en) 1980-04-03 2009-09-15 Biogen Idec Ma Inc. DNA sequences, recombinant DNA molecules and processes for producing human fibroblast interferon-like polypeptides
CN113740408A (zh) * 2020-05-28 2021-12-03 塞莫费雪科学（不来梅）有限公司 用于确定ms扫描数据中的干扰、过滤离子并对样品进行质谱分析的方法和装置

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3256152A (en) * 1965-06-14 1966-06-14 Merck & Co Inc Concentration and purification of interferons, viral inhibiting substances (vis), viral inhibiting factors (vif), or viral inhibitory material
US3385757A (en) * 1962-11-23 1968-05-28 Ici Ltd Quantitative hemadsorption assay technique for the estimation of interferon
US3629235A (en) * 1969-02-12 1971-12-21 Merck & Co Inc Process for isolating an interferon inducer and the product per se
US3800035A (en) * 1971-12-07 1974-03-26 Smithkline Corp Production of interferon from human leukocytes in the absence of serum
US4061538A (en) * 1973-04-04 1977-12-06 Sandoz Ltd. Enzymatically oxidizing interferon
US4184917A (en) * 1974-04-01 1980-01-22 Sandoz Ltd. Process for producing a structurally modified interferon

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3385757A (en) * 1962-11-23 1968-05-28 Ici Ltd Quantitative hemadsorption assay technique for the estimation of interferon
US3256152A (en) * 1965-06-14 1966-06-14 Merck & Co Inc Concentration and purification of interferons, viral inhibiting substances (vis), viral inhibiting factors (vif), or viral inhibitory material
US3629235A (en) * 1969-02-12 1971-12-21 Merck & Co Inc Process for isolating an interferon inducer and the product per se
US3800035A (en) * 1971-12-07 1974-03-26 Smithkline Corp Production of interferon from human leukocytes in the absence of serum
US4061538A (en) * 1973-04-04 1977-12-06 Sandoz Ltd. Enzymatically oxidizing interferon
US4184917A (en) * 1974-04-01 1980-01-22 Sandoz Ltd. Process for producing a structurally modified interferon

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7588755B1 (en) 1980-04-03 2009-09-15 Biogen Idec Ma Inc. DNA sequences, recombinant DNA molecules and processes for producing human fibroblast interferon-like polypeptides
CN113740408A (zh) * 2020-05-28 2021-12-03 塞莫费雪科学（不来梅）有限公司 用于确定ms扫描数据中的干扰、过滤离子并对样品进行质谱分析的方法和装置

Also Published As

Publication number Publication date
EP0031381A1 (fr) 1981-07-08

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